Dietary effects to the local immune response and the initiation and propagation of diabetes and cardiovascular disease in mice

Summary

Background: Longitudinal studies have demonstrated a two-¬way relationship between diabetes and the local inflammatory host response, e.g. periodontitis, with more severe periodontal tissue destruction in diabetic patients and poorer glycemic control in diabetic subjects with periodontal disease. The same association has been described for cardiovascular and periodontal disease. A direct causal relationship is postulated in which advanced glycosylation end products or serum amyloid A increase local and systemic inflammatory phenotypes. Currently, it is unknown how the metabolic status affects local and systemic immune responses and how they are affected by different genetic backgrounds, or diverse microbial communities. Aim: The proposed research project will test the hypotheses that (A) the local immune response in animals largely depends on the genotype irrespectively of the diet and (B) establishing the gut and oral microbiome of high-inflammatory responders into low-inflammatory responders dramatically change the systemic and local immune response. Methods: WP 1: Mice strains with genetically different backgrounds will be used. They will be fed either a high- or low- fat diet for 4 weeks. After 4 weeks ligatures will be placed around the 2nd molars. The oral pathogen P. gingivalis will be applied by oral gavage over a period of 4 weeks. Blood will be collected at different time points to follow systemic inflammation, insulin resistance, and concentrations of AGE, CRP SAA and IL-6. Mice will be scarified after 8 weeks and the severity of the local immune response will be characterised by the amount of bone loss, bone density and detection of inflammatory mediators. WP 2: Those strains with the lowest and largest local immune response will be used for this work package. Mice will be fed either a high- or low- fat diet for 4 weeks. After 4 weeks bacteria will be eradiated from the animals by antibiotic treatment and the oral and gut microbiomes will be exchanged as described elsewhere. Ligatures will be placed around the 2nd molars and the procedures will be equal to WP1.

Supervisor(s)

Research Location

Program Type

PHD

Synopsis

To evaluate the interplay between diet, genotype and microbiome in metabolic diseases and inflammatory host response.

Additional Information

These studies will contribute to the understanding how diet, genotype and microbiome interact in local and systemic inflammatory diseases. This understanding will enable preventive actions aimed to reduce adverse effects of metabolic diseases.